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- Title
4-Methylumebelliferone Enhances Radiosensitizing Effects of Radioresistant Oral Squamous Cell Carcinoma Cells via Hyaluronan Synthase 3 Suppression.
- Authors
Hasegawa, Kazuki; Saga, Ryo; Ohuchi, Kentaro; Kuwahara, Yoshikazu; Tomita, Kazuo; Okumura, Kazuhiko; Sato, Tomoaki; Fukumoto, Manabu; Tsuruga, Eichi; Hosokawa, Yoichiro
- Abstract
Radioresistant (RR) cells are poor prognostic factors for tumor recurrence and metastasis after radiotherapy. The hyaluronan (HA) synthesis inhibitor, 4-methylumbelliferone (4-MU), shows anti-tumor and anti-metastatic effects through suppressing HA synthase (HAS) expression in various cancer cells. We previously reported that the administration of 4-MU with X-ray irradiation enhanced radiosensitization. However, an effective sensitizer for radioresistant (RR) cells is yet to be established, and it is unknown whether 4-MU exerts radiosensitizing effects on RR cells. We investigated the radiosensitizing effects of 4-MU in RR cell models. This study revealed that 4-MU enhanced intracellular oxidative stress and suppressed the expression of cluster-of-differentiation (CD)-44 and cancer stem cell (CSC)-like phenotypes. Interestingly, eliminating extracellular HA using HA-degrading enzymes did not cause radiosensitization, whereas HAS3 knockdown using siRNA showed similar effects as 4-MU treatment. These results suggest that 4-MU treatment enhances radiosensitization of RR cells through enhancing oxidative stress and suppressing the CSC-like phenotype. Furthermore, the radiosensitizing mechanisms of 4-MU may involve HAS3 or intracellular HA synthesized by HAS3.
- Subjects
SQUAMOUS cell carcinoma; HYALURONIC acid; CANCER stem cells; CANCER relapse; DISEASE relapse; OXIDATIVE stress
- Publication
Cells (2073-4409), 2022, Vol 11, Issue 23, p3780
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells11233780